A mass spectrometer (MS) is a device that filters gaseous ions according to their mass-to-charge (m/z) ratio and measures the relative abundance of each ionic species. Mass spectrometry is particularly attractive for in-situ analysis, due to its inherent speed, excellent sensitivity, molecular selectivity, and capability for continuous real-time measurements. A typical mass spectrometer comprises an ion source, wherein the ions are generated; a mass filter, wherein the ions are separated in space or in time; an ion detector, wherein the filtered ions are collected and their relative ion abundance measured; a vacuum system; and means to power the spectrometer. Depending on the type of sample and the method of introducing the sample into the mass spectrometer, ions can be generated in the ion source by electron impact ionization, photoionization, thermal ionization, chemical ionization, desorption ionization, spray ionization, or other processes. Mass spectrometers are generally classified according to the method on which mass filtering is accomplished using electric and/or magnetic fields. Mass filter types include magnetic-sector, time-of-flight, linear quadrupole, ion cyclotron resonance, and ion traps. Detection of ions is typically accomplished by a single-point ion collector, such as a Faraday cup or electronic multiplier, or a multipoint collector, such as an array or microchannel plate collector, whereby all of the ions arrive at the collector simultaneously.
Mass spectrometer performance is generally given in terms of mass range, resolution (i.e., resolving power), and sensitivity of the instrument. Mass range is the lowest and highest masses that can be measured. A large mass range is desired for the analysis of high molecular weight organic and biological analytes. Resolution measures the ability of the instrument to separate and identify ions of slightly different masses. Typically, the resolution for singly charged ions is given by
                    R        =                  m                      Δ            ⁢                                                  ⁢            m                                              (        1        )            where m is the mass of an ion peak in atomic mass units and Δm is the width of the peak at some peak height level (e.g., half peak height). In many cases, the minimum resolution required is such that a molecular ion can be resolved from an adjacent peak having a unit mass difference. According to this requirement, the resolution R should be at least 100 for a chemical species having a nominal mass of 100. High-resolution instruments, required for organic mass spectrometry, can detect peaks separated by fractions of a mass unit. Sensitivity is a measure of the instrument's response to ions of an arbitrary m/z ratio for a particular sample. Sensitivity is typically a function of the efficiency of the ion source and ion detector, as well as the analyzer method used. The sensitivity limit, or detection limit, is the minimum amount of a sample that can be detected under a given set of experimental conditions and distinguished from the instrument noise level and background. Resolution and sensitivity are approximately inversely related to each other. Other important characteristics of a spectrometer instrument include overall size, operating pressure, voltage, and power consumption.
Mass spectrometers can be used for chemical sensing. Analyzing mixtures may be difficult when the mass spectrometer is used alone, since the resulting mass spectrum would be a complex summation of the spectra of the individual components. Therefore, analytical techniques combining the separation methods of gas chromatography and mass spectrometry are often used for chemical sensing. A gas chromatograph (GC) separates volatile mixtures into their component chemical species, which are eluted from a long capillary. The eluents can then be transferred into a mass spectrometer to obtain a mass spectrum of each of the separated components, from which the molecular structure of the individual component species can be inferred. The GC/MS is therefore capable of separating highly complex mixtures, identifying the components, and quantifying their amounts. Alternatively, tandem (MS/MS) or multistage (MSn) mass spectrometers can be combined, wherein one of the mass spectrometers is used to isolate individual ions according to their m/z ratio, and the other is used to examine the fragmentation products of the individual ions. Thus, multiple stages of mass analysis can be obtained in a single analyzer.
Recently, there has been a growing interest in miniature mass spectrometers that enable reduced size, power requirements, vacuum system demands, cost, and complexity. The effect of miniaturization on performance depends on the method of mass analysis. For most methods, mass range and resolution decrease with miniaturization. However, sensitivity may be improved, while power and pumping requirements may be reduced compared to conventional instruments. In particular, the smaller dimensions of miniature analyzers reduces the number of collisions that the ion makes with background gases due to the reduced distance of travel. Therefore, operating pressure requirements may be relaxed with miniaturization. See E. R. Badman and R. G. Cooks, “Miniature mass analyzers,” J. Mass Spectrometry 35, 659 (2000).
Magnetic-sector instruments deflect ions, traveling at constant velocity in a perpendicular magnetic field, along a curved path thereby dispersing them in space according to their m/z values. Alternatively, the magnetic field of the sector can be scanned to sweep the ions across a point detector. Sector mass spectrometers can have high resolution and high mass accuracy, even for high-energy analysis. However, quite large magnetic fields, on the order of tens of Tesla, are required to maintain resolution and detectable mass range as the size of the sector is reduced. Therefore, magnetic-sector instruments are not well-suited to miniaturization.
In a time-of-flight (TOF) mass spectrometer, ions are accelerated to approximately constant kinetic energy in a pulse and allowed to drift down a long flight tube. The TOF mass spectrometer thereby enables temporal discrimination of ions according to their flight time, which is determined by their m/z ratio. Conventional TOF mass spectrometers typically have a high mass range, short analysis time, and are relatively low cost. However, for miniaturized TOF mass spectrometers, the accelerating voltage must be decreased to maintain mass range as the drift length is reduced, seriously degrading resolution.
Linear quadruple mass spectrometers (QMS) filter ions by passing them through tuned radiofrequency (rf) and direct current (dc) electrical fields defined by four, symmetrically parallel quadrupole rods. The QMS permits only those ions with a stable trajectory, determined by their m/z ratio, to travel along the entire length of the central axis of the rod assembly without being deflected out of the intra-rod space. Ions with different m/z ratios can be scanned through the QMS by continuously varying the field between the quadrupole rods. Therefore, the QMS is a variable bandpass filtering ion optic. Miniature linear quadrupoles require lower drive voltages and higher rf drive frequencies to filter heavier ions and maintain resolution as the electrode dimensions decrease. The relative dimensional and positional precision of the parts must be maintained as their size is reduced, although the rod length remains large, relative to the aperture, to provide adequate filtering. However, the QMS is relatively pressure intolerant and can operate effectively at relatively high pressures (e.g., 10−4 Torr). Therefore, they are more amenable to miniaturization due to the avoidance of bulky vacuum pumping systems.
A three-dimensional analogue of the linear QMS is the quadrupole ion trap (QIT), or Paul trap. Like the linear quadrupole, the QIT can control the stability of ion motion in an electric field and can therefore be used for mass analysis. The QIT comprises a central, donut-shaped hyberboloid ring electrode and two hyperbolic endcap electrodes. In normal usage, the endcaps are held at ground potential, and the rf oscillating drive voltage is applied to the ring electrode. Ion trapping occurs due to the formation of a trapping potential well in the central intraelectrode volume when appropriate time-dependent voltages are applied to the electrodes. The ions orbit in the trap and are stabilized or destabilized as the trapping conditions are changed. With mass-selective ejection of ions, the ions become unstable in the axial direction of the well and are ejected from the trap in order of ascending m/z ratio as the rf voltage applied to the ring is ramped. The ejected ions can be detected by an external detector, such as an electron multiplier, after passing through an aperture in one of the endcap electrodes. Like the QMS, ion traps have the advantage of being able to operate at higher pressures. Indeed, a background pressure of a light buffer gas (e.g., 10−3 Torr of helium) is often used to collisionally “cool” the kinetic energy of the trapped ions to achieve coherence, thereby improving the mass resolution and sensitivity of the analyzed ions.
Unlike most other methods of mass analysis, a decrease in the dimensions of the QIT allows trapping of higher m/z ratio ions for fixed operating parameters. Alternatively, for a given m/z ratio, the voltage required to eject ions is reduced quadratically with the linear trap dimension, enabling lower voltages to be used to analyze the same mass range. Like the linear quadrupole, the drive frequency of the QIT must be increased to maintain resolution as the spectrometer dimensions are decreased. The major problem with the miniature ion trap is that the ion storage capacity of the trap decreases with size, reducing the dynamic range and sensitivity.
A cylindrical ion trap (CIT), comprising planar endcap electrodes and a cylindrical ring electrode, rather than hyperbolic electrode surfaces, produces a field that is approximately quadrupolar near the center of the trap. Therefore, CITs have been found to provide performance comparable to QITs. Moreover, the CIT is favored for miniature ion storage and mass analysis devices, because CITs are relatively simple and can be easily machined. Arrays of miniature CITs, with trap dimensions on the order of a millimeter, have been manufactured using precision machining to regain a portion of the lost storage capacity and thereby improving sensitivity. See U.S. Pat. No. 6,762,406 to Cooks et al., which is incorporated herein by reference.
The inner radius r0 of the trapping ring electrode determines the m/z ratio of the trapped ions. Therefore, variable r0 parallel arrays of miniature CITs, each individual trap having a proportionately different size, can be configured to simultaneously trap and monitor different-sized ions. A low-resolution spectra of a multiple ion sample can be obtained from such a variable r0 parallel array by simultaneously ejecting the trapped ions with a dc pulse, without the need to scan the applied rf voltage. The ejected ions can be detected with a position-sensitive detector, resulting in a reduced power requirement and simplification of the ion trap control electronics. See Badman et al., “Cylindrical Ion Trap Array with Mass Selection by Variation in Trap Dimensions,” Anal. Chem. 72(20), 5079 (2000).
Alternatively, the use of multiple traps in a single r0 parallel array can offset some of the loss in ion storage capacity with miniaturization. In the standard mass-ejection analysis mode, parallel arrays of miniature CITs having the same trap dimensions can be scanned to provide simultaneous ejection of similar ions from all traps, providing improved sensitivity. See Badman et al., “A Parallel Miniature Cylindrical Ion Trap Array,” Anal. Chem. 72(14), 3291 (2000).
Serial arrays of such miniature CITs can be also be used for ion storage, mass selection, and ion reaction and product ion analysis. For example, serial arrays of miniature CITs, wherein ions trapped in a first CIT are transferred to a second CIT, can be used to provide multiple stages of mass isolation and analysis in a tandem MS/MS or multistage MS capability. See Z. Ouyang et al., “Characterization of a Serial Array of Miniature Cylindrical Ion Trap Mass Analyzers,” Rapid Comm. Mass Spect. 13, 2444 (1999).
However, prior precision machining methods only provide arrays of miniature CITs comprising a few millimeter-sized traps. Furthermore, bulk micromachining techniques, whereby holes are etched in a semiconductor body or wafer, provide traps with trap dimensions comparable to the wafer thickness (i.e., tens to hundreds of microns). These relatively large traps are not well suited for truly field portable, handheld microanalytical systems. Such microanalytical systems, which have been termed “chemical laboratories on a chip,” are being developed to enable the rapid and sensitive detection of particular chemicals, including pollutants, high explosives, and chemical warfare agents. These microanalytical systems should provide a high degree of chemical selectivity to discriminate against potential background interferents, be able to perform the chemical analysis on a short time scale, and consume low amounts of electrical power for prolonged field use. See C. D. Mowry et al., “Field testing and new applications of gas phase miniature chemical analysis systems,” Proc. 6th Int. Sym. Micro Total Analysis Systems, Nara, Japan, Kluwer Academic Publishers, p. 521 (2002).